New Methods in Peptide Synthesis. I. Tritylsulfenyl and o-Nitrophenylsulfenyl Groups as N-Protecting Groups

Abstract

N-Tritylamino acid p-nitrophenyl esters, with the exception of the glycine derivative, do not couple with amino acid esters. On the other hand, N-tritylsulfenyl (TRS) or N-o-nitrophenylsulfenyl (NPS) amino acid p-nitrophenyl esters show no steric hindrance and have been used to synthesize N-protected dipeptide esters. The N-o-nitrophenylsulfenyl derivatives of L-amino acids themselves have also been prepared and isolated in the pure state as their dicyclohexylammonium (DCHA) salts. These salts have been used directly for peptide synthesis. The TRS or NPS group can be easily removed from N-protected peptides by means of two equivalents of hydrogen chloride in methanol or nonpolar solvents, with the generation of TRS or NPS chloride. The use of the N-sulfenyl protecting groups is advantageous for the lengthening of a peptide chain, especially when the peptide includes amino acids bearing protected functional groups in their side chain. © 1963, American Chemical Society. All rights reserved.